Ординатура / Офтальмология / Английские материалы / Diabetes and Ocular Disease Past, Present, and Future Therapies 2nd edition_Scott, Flynn, Smiddy_2009
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64 Diabetes and Ocular Disease
VEGF production is not unique to diabetic retinopathy, and is also increased in retinopathy of prematurity and other ocular neovascular processes, as well as in physiologic conditions (menstruation and wound healing) and in pathologic vascularization (tumors) throughout the body. The control of retinal angiogenesis is complex, and the molecular puzzle is still being unraveled [94]. Vitreous collagen crosslinking via nonenzymatic glycosylation may contribute to vitreous contraction.
WHY DO PERSONS WITH RETINOPATHY LOSE VISION?
Most ophthalmologists relate vision loss in persons with diabetic retinopathy to vascular changes seen in eyes with DME and PDR. However, studies detailed in this chapter indicate that multiple insults may contribute to visual loss. These changes may be categorized into abnormalities of the media and neurosensory system, with the latter subdivided into vascular and neural alterations, as shown in Table 4.6. A systematic approach to analysis of vision impairment in diabetes provides the best opportunity to maximize visual recovery by restoring optical, vascular, neural, and structural abnormalities. However, overlapping cellular mechanisms contribute to macular edema and other lesions because the vascular and neural elements of the retina are integrally linked. With the exception of media opacities, the final common pathway of vision loss in all cases includes neural dysfunction [95].
The mechanisms by which persons with diabetes lose sight underlie efforts to preserve vision. Clearly, it is benef icial to minimize retinal vascular leakage by laser photocoagulation, steroids or similar means. However, these therapies do not fully protect neuronal and glial cell function. Future treatments based on improved understanding of the complex biology of the retina that support the integrity of the whole retina may provide the best opportunity for persons with diabetes to maintain their vision.
Table 4.6. Mechanisms of Visual Loss in Diabetes Iterations in Ocular Media
Cornea: epithelial erosions
Lens: transient swelling associated with poor metabolic control; cataract
Vitreous: vitreous hemorrhage
Alterations in Neurosensory System
Retina:
Vascular: macular edema or ischemia
Neural: neuronal degeneration as direct effect of diabetes or secondary to vascular occlusion: macular heterotopia; traction or rhegmatogenous retinal detachment
Optic nerve:
Vascular: diabetic papillopathy; nonarteritic anterior ischemic optic neuropathy
Neural: axonal degeneration secondary to diabetes or to vascular lesions
Pathogenesis of Diabetic Retinopathy |
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CONCLUSIONS
Many steps in the pathogenesis of diabetic retinopathy are under intensive investigation. Diabetic retinopathy involves both vascular and neural elements of the retina from the early stages of diabetes through the development of PDR. Improved means of preventing visual loss in diabetes depend on a better understanding of the underlying mechanisms and the altered relationships between the neural retina and blood vessels.
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5
Epidemiology and Risk Factors of
Diabetic Retinopathy
TIEN Y. WONG, MD, PHD,
RONALD KLEIN, MD, MPH,
AND BARBARA E.K. KLEIN, MD, MPH
CORE MESSAGES
•Diabetic retinopathy is the leading cause of blindness among persons aged 20 to 64 years in the United States.
•In adult type 2 diabetic persons 40 years and older, 40% have retinopathy, and about 8% have vision-threatening disease (pre-proliferative retinopathy, proliferative retinopathy or macular edema).
•Incidence rates for new retinopathy signs vary from 5% to 10% per year, and are associated primarily with diabetes duration and glycemic control.
•Hyperglycemia, hypertension, and hyperlipidemia are independent risk factors for the presence, development, and progression of diabetic retinopathy. These factors should be monitored and controlled rigorously in the diabetic patient to prevent visual loss.
•Comprehensive, regular dilated eye examinations are important for early detection of potentially vision-threatening retinopathy.
Diabetes mellitus is a leading cause of morbidity and mortality in the United States [1]. Diabetic retinopathy is the most common specif ic complication of diabetes and is the leading cause of blindness among persons aged
20 to 64 years [2].
Epidemiological studies and clinical trials over the past 25 years have provided data on the prevalence, incidence, and natural history of retinopathy and its associated risk factors [3–5]. Although these findings have been used to develop guidelines for patient care around the world [2,6], considerable morbidity associated with diabetic retinopathy remains. The purpose of this chapter is to review the epidemiology and risk factors of diabetic retinopathy, and their relationship to systemic morbidity and mortality.
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72 Diabetes and Ocular Disease
EPIDEMIOLOGY
Prevalence of Diabetic Retinopathy in the United States. There have been several epidemiological studies on the prevalence of diabetic retinopathy in the United States (U.S.). One of the largest, the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR), assessed both the prevalence and long-term incidence of retinopathy in a population-based cohort of white persons with diabetes residing in an 11-county area in Wisconsin in the 1980s and 1990s [7–9]. The WESDR used stereoscopic fundus photographs of seven standard fields to detect and grade retinopathy based on a modification of the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol. Two groups of individuals were examined: persons diagnosed with diabetes before 30 years of age on insulin treatment (the younger-onset group) and those diagnosed after the age of 30 years (the older-onset group).
In the younger onset group, 71% had retinopathy (defined as microaneurysms only, or retinal hemorrhages or cotton wool spots in the absence of microaneurysms), 23% had proliferative retinopathy and 6% had clinically significant macular edema (CSME) (Fig. 5.1) [8,10]. The likelihood of retinopathy was strongly related to duration of diabetes, and the prevalence ranged from 2% among participants with less than 2 years of diabetes to 98% in those with 15 years or more of disease [8]. The prevalence of proliferative retinopathy ranged from 4% among participants with 10 years of diabetes to 56% in those with 20 or more years of disease [8].
In the older-onset group, retinopathy affected 39% of those who were not on insulin treatment and 70% of those on insulin treatment. Among older-onset participants not on insulin treatment, 3% had proliferative disease and 4% had CSME, but among those on insulin treatment, 14% had proliferative retinopathy and 11% had CSME [9,10]. As in the younger onset group, the prevalence of retinopathy was strongly related to duration of disease, and ranged from about 20% among participants with less than 2 years of diabetes to more than 60% in those with 15 years or more of diabetes.
Other studies conducted within the U.S. have reported on the prevalence of diabetic retinopathy in different populations and settings [11–21]. Variations in study design, population characteristics, definitions of diabetes, and in the ascertainment of retinopathy, however, make it difficult to compare rates directly across these studies. A recent pooled study examined the prevalence of retinopathy among people 40 years and older from eight population-based studies, including the WESDR [22]. The studies included in this meta-analysis used standardized methods to grade retinopathy from fundus photographs and estimated an overall prevalence of retinopathy of about 40% and a prevalence of sight-threatening disease (either pre-proliferative retinopathy, proliferative retinopathy, or macular edema) of about 8%. Thus, based on these estimates, approximately 4 million individuals with diabetes 40 years of age or older in the U.S. have retinopathy, with 900,000 having sight-threatening retinopathy.
Prevalence of Diabetic Retinopathy in Other Countries. There are fewer populationbased data on the prevalence of retinopathy outside of the U.S. [23–33]. In general,
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Older-onset taking insulin 
Older-onset no insulin
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characteristics |
characteristics |
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or worse |
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Figure 5.1. Prevalence and Severity of Retinopathy and Macular Edema at the Baseline Examination, the Wisconsin Epidemiologic Study of Diabetic Retinopathy, 1980–1982. (Source: Modified from Klein R, Klein BEK, Moss SE, et al: The Wisconsin Epidemiologic Study of Diabetic Retinopathy, IX: Four-year incidence and progression of diabetic retinopathy when age at diagnosis is less than 30 years. Arch Ophthalmol. 1989;107:237–243; and Klein R, Klein BEK, Moss SE, et al. The Wisconsin Epidemiologic Study of Diabetic Retinopathy, X: Four-year incidence and progression of diabetic retinopathy when age at diagnosis is 30 years or more. Arch Ophthalmol. 1989;107:244–249. Copyrighted © 1989 with permission from American Medical Association. All rights reserved.)
however, these studies show a similar pattern in both the prevalence and risk factors of diabetic retinopathy. There have been a number of epidemiological studies in England and Europe [23,27–30]. A population-based survey of diabetic patients in Melton Mowbray, England, evaluated the prevalence of retinopathy in insulintreated [29] and non-insulin treated patients [30]. For insulin-treated patients, the prevalence of any retinopathy was 41%. For non-insulin treated patients, the prevalence of retinopathy was 52%. Data from western Scotland showed the prevalence of any diabetic retinopathy to be 26.7% and that of serious retinopathy (defined as maculopathy, pre-proliferative, or proliferative retinopathy) to be about 10% [31]. Studies from Danish populations have shown an overall prevalence of retinopathy of 77% in men and 74% in women with type 1 diabetes [32]. Variations in the prevalence of retinopathy may be due in part to differences in population selection and in methods for assessing retinopathy.
In Australia, three large population-based studies assessed diabetic retinopathy from a standardized grading of fundus photographs. The Melbourne Visual Impairment Project reported a retinopathy prevalence of 29.1% among persons aged 40 years or older with self-reported diabetes.24 The prevalence of untreated, vision-threatening retinopathy in this population was 2.8%. The Blue Mountains Eye Study, west of Sydney, found a similar retinopathy prevalence of 32.4% among older persons aged 49 years and above with known or newly diagnosed